Is Optic Disc Size a Risk Factor for Glaucoma?

Understanding the characteristics of normal optic discs is necessary for assessing glaucomatous changes in the optic nerve. However, the appearance and size of the optic disc varies widely among healthy individuals.

In studies using planimetric measurements from color photographs, the optic disc area was found to range from 0.8 mm2 to >6.0 mm2 in a healthy white population. These values have a Gaussian distribution with a mean of 2.7 ± 0.7 mm2, and may vary according to the study population and method of measurement.1 Studies performed with confocal scanning laser ophthalmoscopy, compared with planimetry, usually produce smaller values for optic disc areas in healthy eyes. One study found a mean disc area of 1.8 mm2 using the Heidelberg Retina Tomograph (HRT, Heidelberg Engineering) confocal scanning laser ophthalmoscope.2 Optical coherence tomography (OCT) yields values similar to HRT.3

Population Differences

Normal optic disc size varies by racial group. The Baltimore Eye Survey analyzed topographic characteristics of the optic disc in 3,387 individuals and found mean optic disc area to be 2.94 mm2 in African Americans compared with 2.63 mm2 in whites, as obtained by planimetry.4 The African Descent and Glaucoma Evaluation Study (ADAGES) found a mean disc area of 2.06 mm2 in African Americans compared with 1.77 mm2 in whites using confocal scanning laser ophthalmoscopy measurements.5

Larger optic disc size combined with higher prevalence of glaucoma in the African American population have led to the hypothesis that eyes with large optic discs would be more prone to glaucoma. Larger optic discs could be less resistant to IOP effects. However, several studies have shown that optic disc area in eyes with primary open-angle glaucoma (POAG) is similar to that of normal eyes.6-8

In studies comparing both eyes of patients with glaucoma, the eye with the larger optic disc showed neither more nor less damage than the contra-lateral eye, indicating that damage is not associated with optic disc size in a particular individual.9-11 In the Baltimore Eye Survey, optic disc size in patients with glaucoma was slightly larger than in healthy individuals. However, after adjusting for confounding factors, the difference between optic disc areas was not statistically significant.

Risk Factor Studies

A few longitudinal studies have evaluated whether optic disc area is a risk factor for glaucoma development or progression. One evaluated 763 eyes of 416 white subjects with ocular hypertension or POAG followed for an average of 67 months.12 Progressive visual field loss was identified in 13.9% of these eyes. No significant differences were observed between mean optic disc areas of progressors and nonprogressors when evaluated by optic disc morphometry using color photographs (2.75 mm2 vs. 2.72 mm2; P=0.62).

As part of the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study (OHTS), Zangwill and colleagues evaluated baseline topographic optic disc factors associated with risk of converting from ocular hypertension to glaucoma.13 All 865 eyes had optic disc measurements acquired with HRT at baseline and were followed for an average of 7 years. African Americans accounted for 17% of participants. During follow-up, 41 eyes developed POAG. No significant difference in mean disc areas was found between those eyes that converted to glaucoma versus those who did not (1.85 mm2 vs. 1.93 mm2). Optic disc area was not significantly associated with risk of conversion (HR: 0.84 for 0.1 mm2 larger; 95% CI: 0.58 –1.2). In a multivariate model adjusting for other known risk factors, such as age, IOP and central corneal thickness, disc area was also not associated with increased risk of conversion.

Myopia

Longitudinal studies of disc area as a risk factor for glaucoma have generally excluded eyes with high myopia. Optic discs of patients with severe myopia are significantly larger than those of eyes with no refractive error. Using planimetric measurements, researchers found a mean optic disc area of 6.87 mm2 in patients with high myopia refraction error greater than −8 D.14 Myopia has been described as a risk factor for glaucoma, and the risk seems to increase substantially for highly myopic subjects. In a recent meta-analysis, the odds ratio for the association between high myopia and glaucoma was almost 2.5.15 Therefore, the large disc size in subjects with high myopia could contribute to their increased glaucoma risk.

Measuring Optic Discs

Optic discs can be classified according to their size. Vertical and horizontal disc diameter can be obtained during slit lamp examination with a fundocopic lens, applying correction factors according to the lens magnification (Figure 1). However, more important than classifying an optic disc by its size is to understand how the optic disc size relates to the cup and neuroretinal rim areas (Figure 2). The size of the optic disc cup increases with the size of the disc (as more space must accommodate the nerve fibers) so that large discs of healthy eyes may have large cups that can be misdiagnosed as glaucomatous cupping. Glaucomatous eyes with small discs may have cups that appear to be small despite considerable neuroretinal rim loss.

FIGURE

Click here for larger version of Figure.

FIGURE

Click here for larger version of Figure.

In summary, optic disc area does not seem to be an important risk factor for development or progression of glaucoma within the normal size ranges for populations. However, highly myopic eyes may show very large optic discs associated with an increased prevalence of glaucoma, and at least part of the increased risk could be related to a biomechanical disadvantage conferred by disc size.

References

  1. Jonas JB, Gusek GC, Naumann GO. Optic disc, cup and neuroretinal rim size, configuration and correlations in normal eyes. Invest Ophthalmol Vis Sci. 1988;29:1151-1158.
  2. Bowd C, Zangwill LM, Blumenthal EZ, Vasile C, Boehm AG, Gokhale PA, et al. Imaging of the optic disc and retinal nerve fiber layer: the effects of age, optic disc area, refractive error, and gender. J Opt Soc Am A Opt Image Sci Vis. 2002;19:197-207.
  3. Leite MT, Zangwill LM, Weinreb RN, Rao HL, Alencar LM, Sample PA, et al. Effect of disease severity on the performance of Cirrus spectral-domain OCT for glaucoma diagnosis. Invest Ophthalmol Vis Sci. 2010;51:4104-4109.
  4. Varma R, Tielsch JM, Quigley HA, Hilton SC, Katz J, Spaeth GL, et al. Race-, age-, gender-, and refractive error-related differences in the normal optic disc. Arch Ophthalmol. 1994;112:1068-1076.
  5. Girkin CA, Sample PA, Liebmann JM, Jain S, Bowd C, Becerra LM, et al. African Descent and Glaucoma Evaluation Study (ADAGES): II. Ancestry differences in optic disc, retinal nerve fiber layer, and macular structure in healthy subjects. Arch Ophthalmol. 2010;128:541-50.
  6. Quigley HA, Hohman RM, Addicks EM, Massof RW, Green WR. Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. Am J Ophthalmol. 1983;95:673-91.
  7. Jonas JB, Gusek GC, Naumann GO. Optic disc morphometry in chronic primary open-angle glaucoma. I. Morphometric intrapapillary characteristics. Graefes Arch Clin Exp Ophthalmol. 1988;226:522-530.
  8. Caprioli J, Miller JM. Videographic measurements of optic nerve topography in glaucoma. Invest Ophthalmol Vis Sci. 1988;29:1294-1298.
  9. Wang XH, Stewart WC, Jackson GJ. Differences in optic discs in low-tension glaucoma patients with relatively low or high pressures. Acta Ophthalmol Scand. 1996;74:364-367.
  10. Jonas JB, Sturmer J, Papastathopoulos KI, Meier-Gibbons F, Dichtl A. Optic disc size and optic nerve damage in normal pressure glaucoma. Br J Ophthalmol. 1995;79:1102-1105.
  11. Jonas JB, Fernandez MC, Naumann GO. Correlation of the optic disc size to glaucoma susceptibility. Ophthalmology. 1991;98:675-680.
  12. Jonas JB, Martus P, Horn FK, et al. Predictive factors of the optic nerve head for development or progression of glaucomatous visual field loss. Invest Ophthalmol Vis Sci. 2004;45:2613-2618.
  13. Zangwill LM, Weinreb RN, Beiser JA, Berry CC, Cioffi GA, Coleman AL, et al. Baseline topographic optic disc measurements are associated with the development of primary open-angle glaucoma: the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study. Arch Ophthalmol. 2005;123:1188-1197.
  14. Jonas JB, Gusek GC, Naumann GO. Optic disk morphometry in high myopia. Graefes Arch Clin Exp Ophthalmol. 1988;226:587-590.
  15. Marcus MW, de Vries MM, Montolio FG, Jansonius NM. Myopia as a risk factor for open-angle glaucoma: a systematic review and meta-analysis. Ophthalmology. 2011;118:1989-1994 e2.

Understanding the characteristics of normal optic discs is necessary for assessing glaucomatous changes in the optic nerve. However, the appearance and size of the optic disc varies widely among healthy individuals.

In studies using planimetric measurements from color photographs, the optic disc area was found to range from 0.8 mm2 to >6.0 mm2 in a healthy white population. These values have a Gaussian distribution with a mean of 2.7 ± 0.7 mm2, and may vary according to the study population and method of measurement.1 Studies performed with confocal scanning laser ophthalmoscopy, compared with planimetry, usually produce smaller values for optic disc areas in healthy eyes. One study found a mean disc area of 1.8 mm2 using the Heidelberg Retina Tomograph (HRT, Heidelberg Engineering) confocal scanning laser ophthalmoscope.2 Optical coherence tomography (OCT) yields values similar to HRT.3

Population Differences

Normal optic disc size varies by racial group. The Baltimore Eye Survey analyzed topographic characteristics of the optic disc in 3,387 individuals and found mean optic disc area to be 2.94 mm2 in African Americans compared with 2.63 mm2 in whites, as obtained by planimetry.4 The African Descent and Glaucoma Evaluation Study (ADAGES) found a mean disc area of 2.06 mm2 in African Americans compared with 1.77 mm2 in whites using confocal scanning laser ophthalmoscopy measurements.5

Larger optic disc size combined with higher prevalence of glaucoma in the African American population have led to the hypothesis that eyes with large optic discs would be more prone to glaucoma. Larger optic discs could be less resistant to IOP effects. However, several studies have shown that optic disc area in eyes with primary open-angle glaucoma (POAG) is similar to that of normal eyes.6-8

In studies comparing both eyes of patients with glaucoma, the eye with the larger optic disc showed neither more nor less damage than the contra-lateral eye, indicating that damage is not associated with optic disc size in a particular individual.9-11 In the Baltimore Eye Survey, optic disc size in patients with glaucoma was slightly larger than in healthy individuals. However, after adjusting for confounding factors, the difference between optic disc areas was not statistically significant.

Risk Factor Studies

A few longitudinal studies have evaluated whether optic disc area is a risk factor for glaucoma development or progression. One evaluated 763 eyes of 416 white subjects with ocular hypertension or POAG followed for an average of 67 months.12 Progressive visual field loss was identified in 13.9% of these eyes. No significant differences were observed between mean optic disc areas of progressors and nonprogressors when evaluated by optic disc morphometry using color photographs (2.75 mm2 vs. 2.72 mm2; P=0.62).

As part of the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study (OHTS), Zangwill and colleagues evaluated baseline topographic optic disc factors associated with risk of converting from ocular hypertension to glaucoma.13 All 865 eyes had optic disc measurements acquired with HRT at baseline and were followed for an average of 7 years. African Americans accounted for 17% of participants. During follow-up, 41 eyes developed POAG. No significant difference in mean disc areas was found between those eyes that converted to glaucoma versus those who did not (1.85 mm2 vs. 1.93 mm2). Optic disc area was not significantly associated with risk of conversion (HR: 0.84 for 0.1 mm2 larger; 95% CI: 0.58 –1.2). In a multivariate model adjusting for other known risk factors, such as age, IOP and central corneal thickness, disc area was also not associated with increased risk of conversion.

Myopia

Longitudinal studies of disc area as a risk factor for glaucoma have generally excluded eyes with high myopia. Optic discs of patients with severe myopia are significantly larger than those of eyes with no refractive error. Using planimetric measurements, researchers found a mean optic disc area of 6.87 mm2 in patients with high myopia refraction error greater than −8 D.14 Myopia has been described as a risk factor for glaucoma, and the risk seems to increase substantially for highly myopic subjects. In a recent meta-analysis, the odds ratio for the association between high myopia and glaucoma was almost 2.5.15 Therefore, the large disc size in subjects with high myopia could contribute to their increased glaucoma risk.

Measuring Optic Discs

Optic discs can be classified according to their size. Vertical and horizontal disc diameter can be obtained during slit lamp examination with a fundocopic lens, applying correction factors according to the lens magnification (Figure 1). However, more important than classifying an optic disc by its size is to understand how the optic disc size relates to the cup and neuroretinal rim areas (Figure 2). The size of the optic disc cup increases with the size of the disc (as more space must accommodate the nerve fibers) so that large discs of healthy eyes may have large cups that can be misdiagnosed as glaucomatous cupping. Glaucomatous eyes with small discs may have cups that appear to be small despite considerable neuroretinal rim loss.

FIGURE

Click here for larger version of Figure.

FIGURE

Click here for larger version of Figure.

In summary, optic disc area does not seem to be an important risk factor for development or progression of glaucoma within the normal size ranges for populations. However, highly myopic eyes may show very large optic discs associated with an increased prevalence of glaucoma, and at least part of the increased risk could be related to a biomechanical disadvantage conferred by disc size.

References

  1. Jonas JB, Gusek GC, Naumann GO. Optic disc, cup and neuroretinal rim size, configuration and correlations in normal eyes. Invest Ophthalmol Vis Sci. 1988;29:1151-1158.
  2. Bowd C, Zangwill LM, Blumenthal EZ, Vasile C, Boehm AG, Gokhale PA, et al. Imaging of the optic disc and retinal nerve fiber layer: the effects of age, optic disc area, refractive error, and gender. J Opt Soc Am A Opt Image Sci Vis. 2002;19:197-207.
  3. Leite MT, Zangwill LM, Weinreb RN, Rao HL, Alencar LM, Sample PA, et al. Effect of disease severity on the performance of Cirrus spectral-domain OCT for glaucoma diagnosis. Invest Ophthalmol Vis Sci. 2010;51:4104-4109.
  4. Varma R, Tielsch JM, Quigley HA, Hilton SC, Katz J, Spaeth GL, et al. Race-, age-, gender-, and refractive error-related differences in the normal optic disc. Arch Ophthalmol. 1994;112:1068-1076.
  5. Girkin CA, Sample PA, Liebmann JM, Jain S, Bowd C, Becerra LM, et al. African Descent and Glaucoma Evaluation Study (ADAGES): II. Ancestry differences in optic disc, retinal nerve fiber layer, and macular structure in healthy subjects. Arch Ophthalmol. 2010;128:541-50.
  6. Quigley HA, Hohman RM, Addicks EM, Massof RW, Green WR. Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. Am J Ophthalmol. 1983;95:673-91.
  7. Jonas JB, Gusek GC, Naumann GO. Optic disc morphometry in chronic primary open-angle glaucoma. I. Morphometric intrapapillary characteristics. Graefes Arch Clin Exp Ophthalmol. 1988;226:522-530.
  8. Caprioli J, Miller JM. Videographic measurements of optic nerve topography in glaucoma. Invest Ophthalmol Vis Sci. 1988;29:1294-1298.
  9. Wang XH, Stewart WC, Jackson GJ. Differences in optic discs in low-tension glaucoma patients with relatively low or high pressures. Acta Ophthalmol Scand. 1996;74:364-367.
  10. Jonas JB, Sturmer J, Papastathopoulos KI, Meier-Gibbons F, Dichtl A. Optic disc size and optic nerve damage in normal pressure glaucoma. Br J Ophthalmol. 1995;79:1102-1105.
  11. Jonas JB, Fernandez MC, Naumann GO. Correlation of the optic disc size to glaucoma susceptibility. Ophthalmology. 1991;98:675-680.
  12. Jonas JB, Martus P, Horn FK, et al. Predictive factors of the optic nerve head for development or progression of glaucomatous visual field loss. Invest Ophthalmol Vis Sci. 2004;45:2613-2618.
  13. Zangwill LM, Weinreb RN, Beiser JA, Berry CC, Cioffi GA, Coleman AL, et al. Baseline topographic optic disc measurements are associated with the development of primary open-angle glaucoma: the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study. Arch Ophthalmol. 2005;123:1188-1197.
  14. Jonas JB, Gusek GC, Naumann GO. Optic disk morphometry in high myopia. Graefes Arch Clin Exp Ophthalmol. 1988;226:587-590.
  15. Marcus MW, de Vries MM, Montolio FG, Jansonius NM. Myopia as a risk factor for open-angle glaucoma: a systematic review and meta-analysis. Ophthalmology. 2011;118:1989-1994 e2.